This R01 application proposes functional neuroimaging studies with human subjects to elucidate the role of the prefrontal cortex and amygdala in the processing of facial identities and expressions that predict different social outcomes. Presentations of facial expressions of emotion in neuroimaging studies have proven particularly robust stimuli for activating amygdala and prefrontal regions involved in processing biologically- relevant social cues. Further, these tasks have proven useful for revealing aberrant brain activation patterns in patients with various emotional disorders (e.g., anxiety, depression). Here we propose to further develop our facial expression tasks to increase our understanding of cortical-subcortical interactions during the processing of these socially relevant cues. The utility of this work is that it will provide for a better understanding of the basic rules that determine amygdala responses, and allow us to better understand how the amygdala interacts with reciprocally connected prefrontal areas when such expressions are encountered. The proposed studies comprise programmatic extensions of our previous work as well as incorporate a novel longitudinal study of the effect of regulatory experience on brain structure. This specific study builds off our recent exciting published finding showing that the structural integrity of an amygdala-prefrontal pathway predicts individual differences in reported anxiety. The experiments proposed here are critical for establishing an understanding of the normal pattern of adult human brain responsivity to these ubiquitous social cues. These data will be usefully compared to complementary developmental research (i.e., with children and adolescents) and will be amenable to direct translation to clinical populations. PUBLIC HEALTH RELEVANCE: Facial expressions are everywhere. Indeed, we use the expressions of others on a moment-to-moment basis to predict what will happen next in our social world. The experiments proposed here will increase our understanding of the brain mechanisms involved in this learning. With this information, we can then better understand what goes wrong in the brains of individuals with major depression and anxiety disorders.